Advances in treatment for childhood cancer over the past five decades have resulted in a rapidly growing population of young cancer survivors, a substantial number of whom are adolescent/young adults - the age group at highest risk for sexually transmitted infection. Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States today, with prevalence in young, sexually active individuals ranging from 44.8% in females to 51.2% in males. Persistent infection with oncogenic strains of HPV (e.g., types 16 and 18) is associated with the development of cancers affecting the genital tract and oropharyngeal mucosa. Immunosuppression increases persistence of HPV infection and risk of HPV-related malignancies. Systemic cancer treatment may result in immunosuppression for prolonged periods, placing cancer survivors at higher risk for HPV-related morbidity. The quadrivalent HPV (qHPV) vaccine is indicated for prevention of HPV-related cancers and precancerous or dysplastic lesions in males and females between 9 and 26 years of age. The safety, tolerability, immunogenicity, and efficacy of the qHPV vaccine have been demonstrated in healthy young individuals; however, vaccine uptake to date has been low in the general population and no studies to date have determined vaccine uptake in cancer survivors, or the immunogenicity or safety/tolerability of the qHPV vaccine in this vulnerable population. Thus, there is a critical need to develop evidence to inform optimal uptake and utilization of the HPV vaccine in cancer survivors. This proposal aims to (1) estimate the prevalence of HPV vaccine initiation in cancer survivors 9-26 years of age and examine the sociodemographic, behavioral, and medical determinants of non-initiation; and (2) among non-immunized survivors, evaluate the 3-dose qHPV vaccine series to determine the following: Immunogenicity following the third and final vaccine dose; clinical/host factors influencing immunogenicity; and the safety/tolerability of the qHPV vaccine. Evaluation of the antibody response persistence at 1 and 2 years post-vaccine initiation and clinical/host factors influencing response persistence will be explored. If rates of HPV vaccine initiation are low among cancer survivors, this study will inform development of theory-based interventions to improve vaccine uptake, and identify subgroups likely to derive the most benefit from targeted interventions. This study will also identify clinical factors associated with inadequate immunogenic response to the vaccine and the impact of humoral competence on response, providing a foundation for future development of alternative vaccination strategies in subgroups unable to mount an adequate response to the standard 3-dose series. The proposed research addresses the high priority areas of health promotion, cancer prevention, and cancer survivorship. Importantly, males - a population that has been significantly understudied in regard to HPV vaccination - will be included; and the study will be conducted across four geographically distinct institutions to assure representation from an ethnically and racially diverse cohort of cancer survivors. PUBLIC HEALTH RELEVANCE: Persistent infection with oncogenic strains of the human papillomavirus (HPV) is strongly associated with development of invasive HPV-related malignancies; risk for persistent HPV infection may be increased in young cancer survivors due to treatment-related immunosuppression. The quadrivalent HPV vaccine is indicated for prevention of HPV-related cancers and precancerous lesions in males and females age 9-26, but vaccine uptake, immunogenicity and safety/tolerability have not been determined in cancer survivors. This proposal will comprehensively evaluate the HPV vaccine (uptake, immunogenicity, and safety/tolerability) in cancer survivors, identifying barriers/facilitators to vaccination and factors associated with inadequate immunogenic response, thus providing the needed evidence base for vaccine recommendations, and promoting primary prevention of HPV-related malignancies and their associated morbidity and mortality in this vulnerable population.